Abstract
Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (−50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (−39%, −54% and −76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis.
Highlights
Inflammation is biochemically modulated by oxylipins cooperating with cytokines and chemokines[11]
Includes bioactive, oxidized lipid mediators synthesized from free omega-6 polyunsaturated fatty acids (n-6 PUFA) including arachidonic acid (AA), linoleic acid (LA), and dihomo-gamma-linolenic acid (DGLA), or omega-3 polyunsaturated fatty acid (n-3 PUFA) including eicosapentenoic acid (EPA), docosahexanoic acid (DHA), and alpha-linolenic acid (ALA)
We report limited systemic inflammation in women with endometriosis and the results was corroborated with the non-specific inflammation marker, C-reactive protein[15]
Summary
Inflammation is biochemically modulated by oxylipins cooperating with cytokines and chemokines[11]. The n-6 PUFAs AA and LA are the precursors of pro-inflammatory lipid mediators while EPA and DHA derived lipid mediators resolve inflammation[12]. We previously employed a targeted lipidomics approach using a liquid chromatography-tandem mass spectrometry (LC-MS/ MS) to analyze serum sphingolipids in endometriosis[14] and we employed a combined targeted ‘omics approach comprising LC-MS/MS and multiplex immunoassay to assess the levels of serum pro-inflammatory oxylipins, cytokines and chemokines. We report limited systemic inflammation in women with endometriosis and the results was corroborated with the non-specific inflammation marker, C-reactive protein[15]. Our results inform prospective researchers in the search for biomarker discovery of endometriosis diagnosis to refrain from pro-inflammatory mediators in the circulation
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